The present invention relates to novel compositions of non-lipophilic ionic inorganic esters of organic compounds. The inventive compositions are useful, for example, for altering the solubility properties of the esters and for providing controlled-delivery systems for pharmaceuticals.
Frequently a physical property of a chemical must be altered to enable its purification or chemical manipulation. This is often accomplished by chemically modifying a functional group on the molecule. For example, an organic acid may be esterified to render it lipid-soluble, or volatile. A primary difficulty with such chemical modifications of biologically important compounds, such as pharmaceuticals, is that the functional group sought to be altered is often involved in the particular compound's biological activity. Thus, changing the compound's structure can destroy its essential biological activity. Accordingly, the search for methods of altering the physical properties of compounds of interest without altering the chemical structure of the compounds is the subject of active and ongoing research.
Such methods for solubilizing lipophilic compounds in water are known. One of these is the creation of dispersible lipid vesicles or micelles into which lipophilic compounds of interest can be incorporated. For example, Steffan, U.S. Pat. No. 4,158,707 discloses the use of micelles comprising cholic acid and certain lipoids as aqueous vehicles suitable for parenteral administration of medicaments which are insoluble in water. These methods require the careful creation of suitable micelles, detailed knowledge of the extent to which the medicament can be incorporated into the micelles and the physical separation of micelles from the unincorporated material.
Certain limited methods for creating lipophilic complexes of non-lipophilic materials also are available. Thus, lipophilic crown ether complexes of metal ions are known, but crown ether complexes of larger, organic molecules do not exist. Development of lipophilic complexes of such non-lipophilic compounds would be highly desirable, and is an object of the present invention.
A further object of this invention relates to the controlled administration of pharmaceuticals, which is often necessary to insure their maximum effectiveness with a minimum of side effects. The concentration of a drug at the target site may be manipulated by many controlled release means, as described in Benson et al., (1982), Pharmaceuticals, Controlled Release, Encyclopedia of Chemical Technology 17, pp. 290-310. Some of these means maintain the concentration of a drug in the bloodstream at a constant level, while others serve to release the drug only to certain organs or tissues. The methods include, for example, delivery modules from which the drug is slowly leached, intravenous drip systems, complex mini-pumping systems placed within the body, and liposome delivery systems. The particular system chosen for delivery of a given pharmaceutical depends upon many factors including the specificity or generality of the drug's site of action, the concentration needed for therapeutic effectiveness, the precision with which a given concentration of the drug must be maintained, and the length of time the optimal dose level must persist. Also important are properties of the pharmaceutical itself as its solubility properties and its stability once released into the bloodstream or tissue. Clearly, modification of the properties of a pharmaceutically effective compound so that it can be administered by a wider range of controlled delivery systems would greatly increase the therapeutic usefulness of the drug.
The present invention provides novel compositions of an ampholytic lipid or polymer, or a suitable non-ampholytic lipid, with a non-lipophilic ionic ester of an organic compound, and methods for making these compositions.
The present invention also provides a composition of a non-lipophilic ionic inorganic ester of an organic compound, the compound having solubility properties which differ from the solubility properties of the ester.
Another embodiment of the present invention provides pharmaceutically effective compositions comprising the novel compounds of interest. The compositions are suitable for controlled delivery of the compounds in a pharmaceutically effective manner.